Sustained inhibition of neovascularization in vldlr(-/-) mice following intravitreal injection of cerium oxide nanoparticles and the role of the ASK1-P38/JNK-NF-kappa B pathway

    Authors

    X. Cai; S. Seal;J. F. McGinnis

    Comments

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    Abbreviated Journal Title

    Biomaterials

    Keywords

    Nanoceria; vldlr(-/-) mouse; Neovascularization; Retinal degeneration; Signal transduction; DENSITY LIPOPROTEIN RECEPTOR; ENDOTHELIAL GROWTH-FACTOR; FACTOR-KAPPA-B; RETINAL ANGIOMATOUS PROLIFERATION; VEGF-INDUCED ANGIOGENESIS; MACULAR; DEGENERATION; SIGNALING PATHWAYS; OXIDATIVE STRESS; MOUSE MODEL; SUBRETINAL NEOVASCULARIZATION; Engineering, Biomedical; Materials Science, Biomaterials

    Abstract

    Cerium oxide nanoparticles (nanoceria) are direct antioxidants; they inhibit pathological neovascularization following a single intravitreal injection into new born very low density lipoprotein receptor knockout (vldlr(-/-)) mice. However, the long-term therapeutic effects and mechanisms of nanoceria action on regression of the existing pathologic neovascularization in the eyes are unknown. We intravitreally injected P28 vldlr(-/-) mice and extended the endpoint for analysis until P70. The data demonstrate that nanoceria sustained their therapeutic function up to 6 weeks. Multiple parameters for nanoceria effects were examined including: regression of existing abnormal blood vessels, reduction of vascular leakage, down-regulation of the expression of vascular endothelial growth factor (VEGF), acrolein, glial fibrillary acidic protein (GFAP) and caspase 3 as well as up-regulation of the expression of rod- and cone-opsin genes. Regulation of ASK1-P38/JNK-NF-kappa B signaling pathway by nanoceria was investigated. Our data demonstrated that a single intravitreal injection of nanoceria in P28 vldlr(-/-) mice produced sustained regression of existing oxidative stress-induced neovascularizations, prevented blood vessel leakage and inhibited apoptosis via down-regulation of the ASK1-P38/JNK-NF-kappa B signaling pathway. (C) 2013 Elsevier Ltd. All rights reserved.

    Journal Title

    Biomaterials

    Volume

    35

    Issue/Number

    1

    Publication Date

    1-1-2014

    Document Type

    Article

    Language

    English

    First Page

    249

    Last Page

    258

    WOS Identifier

    WOS:000328006100024

    ISSN

    0142-9612

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